Researchers unveiled early results from the pilot phase of the 1000 Genomes Project on Wednesday, revealing the most complete inventory to date of the millions of DNA variations between individuals.
The findings are estimated to contain 95 percent of the genetic variation of any person on Earth, and shed light on the genetic roots of diseases and why some people are at greater risk than others for developing illnesses such as diabetes or cancer.
The more subtle genetic variations also offer clues about the diversity of mankind, as well as human evolution and brain development, the researchers said.
Launched in 2008, the 1000 Genomes Project is an international collaboration of hundreds of geneticists working to build a detailed map of human genetic variation. The initiative began with three pilot studies to develop, evaluate and compare strategies for producing the map.
The current findings from the pilot phase were produced using next-generation DNA sequencing technologies to characterize human genetic variations in 179 people representing the continents of Africa, Europe and Asia.
“The pilot studies of the 1000 Genomes Project laid a critical foundation for studying human genetic variation,” said Dr. Richard Durbin of the Wellcome Trust Sanger Institute, a co-chair of the consortium.
“These proof-of-principle studies are enabling consortium scientists to create a comprehensive, publicly available map of genetic variation that will ultimately collect sequence from 2,500 people from multiple populations worldwide and underpin future genetics research.”
Genetic variation between people refers to differences in the order of chemical units, known as bases, which make up the DNA in the human genome. These differences can be as small as a single base being replaced by a different one, or as large as entire sections of a chromosome being duplicated or relocated to another place in the genome. Some of these variations are common in the population, while others are rare.
By comparing many individuals to one another, and by comparing one population to others, the consortium researchers can create a map of all types of genetic variation.
The pilot studies’ findings revealed that humans carry between 250 and 300 genetic changes that would cause a gene to stop functioning normally, and that each person carries between 50 and 100 genetic variations that had previously been associated with an inherited disease.
While no human carries a perfect set of genes, individuals who carry these defective genes will likely remain healthy since each person carries at least two copies of every gene.
In addition to looking at variants that are shared between many people, the researchers also investigated the genomes of six people: two mother-father-daughter nuclear families. By finding new variants present in the daughter but not the parents, the team was able to observe the precise rate of mutations in humans, showing that each person has approximately 60 new mutations that are not in either parent.
With the completion of the pilot phase, the project has moved into full-scale studies in which 2,500 samples from 27 populations will be studied over the next two years.
The project said it seeks to provide a comprehensive public resource that supports research into all types of genetic variation that might cause human disease.
“By making data from the project freely available to the research community, it is already impacting research for both rare and common diseases,” said David Altshuler, Deputy Director of the Broad Institute of Harvard and MIT, a co-chair of the project.
“This is the largest catalog of its kind, and having it in the public domain will help maximize the efficiency of human genetics research,” said Dr. Durbin, referring to the pilot studies’ early results.
Dr. Evan Eichler of the University of Washington in Seattle and colleagues used the findings from the project’s pilot phase to identify subtle differences between individuals in areas of the genome where DNA sequences are often repeated many times.
“I believe this is where we will make huge inroads in understanding the genetic basis of human disease,” Eichler told Reuters.
His findings were published online on Wednesday in the journal Science, and coincide with the publication in the journal Nature of the pilot data from the 1000 Genomes Project.
Eichler said copy number variation, or differences in DNA sequences, has been traditionally hard to compare. However, they may explain why some people have certain diseases while others do not, and why some are more severely affected by disease than others.
Duplications of segments of the genome seem to have resulted in many of the qualities that distinguish human beings from other primate species, and may also be linked with diseases such as autism and schizophrenia, said Eichler during a press briefing.
Advances in machines that sequence genetic information, made by companies such as Roche and Illumina, have allowed researchers to make swift gains in their understanding of variations in human genes, said researchers from the 1000 Genomes Project on Wednesday.
“Already, just in the pilot phase, we’ve identified over 15 million genetic differences by looking at 179 people. Over half of those differences haven’t been seen before,” said Dr. Durbin.
The full-scale 1000 Genomes Project pilot study includes data from more than 800 people, identifying some 16 million previously unknown genetic code variations. Durbin said the new data would help researchers assess the genetic causes of both rare and common genetic diseases.
The 1000 Genome Project is funded through foundations and national governments, and is estimated to cost $120 million from its inception in 2008 through 2012. Data from the pilot studies and the full-scale project are freely available at http://www.1000genomes.org.
The research was also published online October 27, 2010, in the journal Nature. The full report can be viewed at http://www.nature.com/nature/journal/v467/n7319/pdf/nature09534.pdf.
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